1. Field of the Invention
The present invention relates to a device and related method for dispensing small volumes of liquid, and more specifically to such a device and method for simultaneously dispensing liquid from a plurality of liquid dispensing members into a receiving plate.
2. Discussion of the Related Art
Currently, screening programs identify potential compounds for use as drugs. Specifically, drug discovery often depends on high throughput screening (HTS) techniques to screen compounds, such as liquid analytes, as potential drug candidates. In HTS, an increasingly high number of compounds, most often organized in libraries, are tested simultaneously. Simultaneous testing of a high number of compounds is due, at least in part, to technological developments, such as automated testing, combinatorial chemistry, and the polymerase chain reaction. An increased demand for new and better drugs for a variety of diseases also drives the simultaneous testing of a high number of compounds.
The standard library, or plate, for use in HTS has a 96 well per plate format. Thus, HTS systems typically have been developed for use with this format. For increasing throughput requirements and simultaneous testing of more compounds, HTS has been using higher density plates with, for example, 384, 864, 1536, and 9600 wells. These increased density plates present new problems. Particularly, the transfer of compounds into the plate often limits the testing process, as the compounds have to be brought into a high density often at a different geometry. Subsequent dispensing of solutions onto these high density plates during the testing process also poses difficulties. In addition, the introduction of robots and other forms of automation in drug discovery has led to new concerns, such as, for example, concerns regarding the speed, parallelization, volume, and reliability of robotic systems.
Current transfer and dispensing systems often rely on glass pipettors with plungers (such as the Hydrasystem(trademark) of Robin Scientific Inc.), needles or pins, or piezo-electric pipettors. Each such system has drawbacks. For example, current pipetting systems include the relatively high cost of pipet tips, which can be substantial in automated testing. The use of needles and pins for liquid dispensing, although less expensive, lacks control over the dispensed volume and does not provide for multiple replicas to be made. Current piezo-electric pipettors usually provide increased control over dispensed volume but typically are relatively large, difficult to miniaturize, and not suitable for massive parallel dispensing due to their relative expense. Current glass pipettors, although not as expensive, share many of the disadvantages of current piezo electric pipettors and may not dispense liquid in volumes as small as 100 nanoliters.
To overcome the drawbacks of conventional systems and in accordance with the purpose of the invention, the invention comprises a device for dispensing liquid. The device includes a housing configured to contain a plurality of liquid dispensing members containing a liquid and configured to contain a receiving member in a receiving position to receive the liquid from the plurality of liquid dispensing members. The housing defines a first pressure chamber and a second pressure chamber. The first pressure chamber is capable of being sealed relative to the second pressure chamber. The device also includes a differential pressure generator operably connected to at least one of the first and second pressure chambers. The generator is capable of generating a pressure differential between the first and second pressure chambers to cause the plurality of liquid dispensing members to dispense liquid into the receiving member.
According to an embodiment of the inventive device, the first pressure chamber is in fluid communication with ambient environment. According to another embodiment, the device includes a plug to selectively seal the second pressure chamber from the ambient environment. The plug may include a valve in fluid communication with the second pressure chamber.
According to a further embodiment of the device, the housing is configured to hold a first end of each of the plurality of liquid dispensing members in the first pressure chamber and a second end of each of the plurality of liquid dispensing members and the receiving member in the second pressure chamber.
In an even further embodiment of the device, the differential pressure generator is in communication with the second pressure chamber and is capable of creating a pressure in the second pressure chamber that is lower than a pressure in the first pressure chamber.
In another embodiment of the inventive device, the differential pressure generator is in communication with the second pressure chamber and includes a movable member capable of altering a volume of the second pressure chamber to alter a pressure within the second pressure chamber. In an embodiment, the movable member seals the second pressure chamber from ambient environment. The movable member may include a flexible member between a pair of movable plates.
In another embodiment, the device of the present invention includes a support adjacent to the housing and capable of supporting a plurality of receiving members. The support may be movable relative to the housing to position a receiving member in the housing. In an embodiment, the support is moveable relative to the housing to sequentially position receiving members in the housing one receiving member at a time.
In a further embodiment of the device, the second pressure chamber is configured to contain the receiving member and the device includes a positioning device within the second pressure chamber capable of positioning the receiving member in the receiving position. The positioning device may include a movable element having an end capable of gripping the receiving member.
According to another aspect, the invention comprises a device for dispensing liquid that includes a holder having a plurality of liquid dispensing members mounted therein. Each of the plurality of liquid dispensing members is configured to contain a liquid between first and second ends of the dispensing member. In an embodiment, each of the members is configured to contain a different liquid between the first and second ends. A receiving member is capable of receiving liquid dispensed from the plurality of liquid dispensing members. A housing defines a first pressure chamber and a second pressure chamber. The first pressure chamber is capable of being sealed relative to the second pressure chamber. A differential pressure generator is operably connected to at least one of the first and second pressure chambers. The generator is capable of generating a pressure differential between the first and second pressure chambers. The housing is configured to contain the holder in a dispensing position and the receiving member in a receiving position so that the generation of the pressure differential causes the plurality of liquid dispensing members to dispense liquid onto the receiving member.
In an embodiment of the inventive device, the holder seals the first pressure chamber from the second pressure chamber.
In another embodiment, the first pressure chamber is in fluid communication with ambient environment and the second pressure chamber is capable of being selectively sealed from the ambient environment.
In a further embodiment, each of the plurality of liquid dispensing members is a capillary. In an even further embodiment of the inventive device, the housing is configured to contain the holder so that the first end of each capillary is in the first pressure chamber and the second end of each capillary is in the second pressure chamber.
In yet another embodiment of the inventive device, the differential pressure generator is in communication with the second pressure chamber and capable of creating a pressure in the second pressure chamber that is lower than a pressure in the first pressure chamber. According to an embodiment, the differential pressure generator includes a movable member capable of altering a volume of the second pressure chamber to create the pressure within the second pressure chamber. The movable member may seal the second pressure chamber from ambient environment. The movable member also may include a flexible member. According to an embodiment, the flexible member is between a pair of movable plates.
Another embodiment of the inventive device further includes a support adjacent to the housing and capable of supporting a plurality of receiving members. In another embodiment, the support is movable relative to the housing to sequentially position receiving members in the housing one receiving member at a time.
According to a further embodiment of the inventive device, the second pressure chamber is configured to contain the receiving member, and the device further includes a positioning device within the second pressure chamber capable of positioning the receiving member in the receiving position. In an embodiment, the positioning device includes a movable element having an end capable of gripping the receiving member.
According to a further aspect, the invention comprises a method of dispensing liquid from a plurality of liquid dispensing members onto a receiving plate. The method includes the steps of positioning a plurality of liquid dispensing members into a dispensing device so that a first end of each dispensing member is contained in a first pressure chamber of the dispensing device and a second end of each dispensing member is contained in a second pressure chamber of the dispensing device; positioning a receiving plate in the second chamber relative to the second ends of the dispensing members; and creating a pressure differential between the first and second pressure chambers so that the dispensing members dispense liquid into the receiving plate.
According to an embodiment of the method, the creating step includes lowering a pressure in the second pressure chamber. In an embodiment, lowering the pressure in the second pressure chamber includes increasing a volume of the second pressure chamber. The volume may be increased by moving a movable member.
According to another embodiment, the inventive method further includes sealing the first pressure chamber from the second pressure chamber. The sealing step may include positioning a holder of the plurality of liquid dispensing members between the first pressure chamber and the second pressure chamber.
In another embodiment of the inventive method, the first pressure chamber is exposed to an environment, and the method further includes sealing the second pressure chamber from the environment prior to the creating step.
In yet another embodiment, the method further includes, subsequent to the pressure differential creating step, the step of equalizing pressures within the first and second pressure chambers.
An embodiment of the method further includes the steps of removing the receiving plate from the second chamber, and repeating the receiving plate positioning step, the pressure differential creating step, and the pressure equalizing step to dispense liquid onto a subsequent receiving plate.
In a further embodiment of the method each of the plurality of dispensing members is a capillary, the first end is an open top end, and the second end is an open bottom end.
It is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed.